The present invention relates to a method for preventing or treating infection and disease in a mammal caused by a virus. More specifically, the invention relates to the administration of a ganglionic blocking agent to a mammal either before or after the virus has infected the host.
Viruses are associated with a large number of infections and diseases in mammals, such as man. Although modern medical science has developed some treatment techniques that are effective to prevent a particular disease, i.e., the polio vaccine, the art generally lacks a method by which a large number of different virus infections can be effectively prevented or treated.
Past treatments of various diseases caused by viruses have been largely ineffective. To inhibit viral replication, an agent must selectively inhibit one or more of the following specific functions: (1) adsorption, (2) uncoating, (3) transcription, (4) protein synthesis, (5) nucleic acid replication, (6) maturation, and (7) release.
For example, various agents developed in an attempt to treat Herpes Simplex Virus type 1 (HSV-1) and Type 2 (HSV-2), (e.g. idoxuridine, cytosine arabinoside, adenine arabinoside, triflurothymidine, and acyclovir) all interfere with viral and host cellular functions. Because of host cell toxicity, these agents have been of very limited effectiveness for use, especially systemic, in humans to treat or prevent HSV-1 and HSV-2.
Accordingly, there is a strong need for a method that can effectively treat or prevent in a mammal infections and diseases caused by viruses, of which the above-mentioned HSV-1 and HSV-2 are merely examples. Although ganglionic blockers have been known in the art, the art has failed to recognize that ganglionic blockers can effectively treat and prevent in mammals infections and diseases associated with a variety of viruses, including HSV-1 and HSV-2.
Various investigators first described the nicotine paralyzing actions of the tetraethylammonium (TEA) ion on ganglia as early as 1913 and other investigators reported certain additional properties. Nevertheless, the art largely overlooked the TEA ion until Acheson and Moe in 1945 and 1946 and Acheson and Pereira in 1946 published their definitive analyses of the effects of the TEA ion on the cardiovascular system and autonomic ganglia. The pharmacological effects of the TEA ion were then studied in man and applied clinically in a variety of disorders in which reversible sympathetic ganglionic blockade was desired. The subsequent discovery of the ganglionic blocking agent, hexamethonium (HM) ion, however, relegated the TEA ion to a minor status as a diagnostic tool and therapeutic agent.
Various bis-quaternary ammonium salts that were ganglionic blocking agents, such as hexamethonium bromide (HMB), were then developed and studied independently by Barlow and Ing in 1948 and by Paton and Zaimas in 1949. Marked ganglionic blockage was found when the bridge between the two nitrogen atoms has 5 or 6 methylene groups and marked neuromuscular blockage was found when the bridge consisted of 10 to 12 methylene groups.
Various triethylsulfonium salts, such as the monoquaternary and bis-quaternary ammonium ions, also possess ganglionic blocking actions. The synthesis of trimethaphorsulfonate, a ganglionic blocker, occurred in 1949.
Although tetraethylammonium chloride (TEAC), a ganglionic blocker, was briefly advocated for use in the 1950s to treat the pain associated with herpes zoster, this recommendation was subsequently abandoned. Thus, there was no recognition in the art that TEAC could be used to treat infections and diseases caused by a variety of other viruses.
The synthesis of secondary amines with ganglionic blocking activity represented somewhat of a departure in the chemistry of these blocking agents. The pharmacological properties of mecamylamine hydrochloride were first reported in the mid-1950's, and the drug was soon thereafter introduced into therapy. Pempidine was introduced shortly thereafter.
Notwithstanding the long period during which ganglionic blockers have been known and studied, the principal therapeutic use of ganglionic blockers, other than in the present invention, is in the treatment of severe hypertension and hypertensive crisis in humans. However, newer potent agents, such as nitroprusside and diazoxide, have virtually replaced the ganglionic blockers for these uses. Hence, until the present invention, the art has failed to recognize the ability of ganglionic blocking agents to treat or prevent infections and diseases in a mammal caused by a virus.